Injectable cryogel-based whole-cell cancer vaccines.
Bencherif SA1] School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, USA [2] Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, Massachusetts 02115, USA [3] Sorbonne University, UTC CNRS UMR 7338, Biomechanics and Bioengineering (BMBI), University of Technology of Compiègne, BP 20529, Rue Personne de Roberval, Compiègne 60205, France.
Warren Sands R1] School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, USA [2] Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, Massachusetts 02115, USA [3] University of Pittsburgh Medical Center Department of Medicine, Pittsburgh, Pennsylvania 15232, USA.
Ali OA1] School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, USA [2] Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, Massachusetts 02115, USA.
Li WA1] School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, USA [2] Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, Massachusetts 02115, USA.
Lewin SA1] School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, USA [2] Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, Massachusetts 02115, USA.
Braschler TM1] School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, USA [2] Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, Massachusetts 02115, USA [3] School of Engineering, LMIS4, Station 17, École polytechnique fédérale de Lausanne, Lausanne 1015, Switzerland.
Shih TY1] School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, USA [2] Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, Massachusetts 02115, USA.
Verbeke CS1] School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, USA [2] Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, Massachusetts 02115, USA.
Bhatta D1] School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, USA [2] Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, Massachusetts 02115, USA.
Dranoff GDepartment of Medical Oncology and Cancer Vaccine Center, Dana-Farber Cancer Institute and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02215, USA.
Mooney DJ1] School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, USA [2] Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, Massachusetts 02115, USA.
English
A biomaterial-based vaccination system that uses minimal extracorporeal manipulation could provide in situ enhancement of dendritic cell (DC) numbers, a physical space where DCs interface with transplanted tumour cells, and an immunogenic context. Here we encapsulate GM-CSF, serving as a DC enhancement factor, and CpG ODN, serving as a DC activating factor, into sponge-like macroporous cryogels. These cryogels are injected subcutaneously into mice to localize transplanted tumour cells and deliver immunomodulatory factors in a controlled spatio-temporal manner. These vaccines elicit local infiltrates composed of conventional and plasmacytoid DCs, with the subsequent induction of potent, durable and specific anti-tumour T-cell responses in a melanoma model. These cryogels can be delivered in a minimally invasive manner, bypass the need for genetic modification of transplanted cancer cells and provide sustained release of immunomodulators. Altogether, these findings indicate the potential for cryogels to serve as a platform for cancer cell vaccinations.